CAREER: Illuminating Emergent Microbial Interactions via Modular Synthetic Consortia

微生物群落对人类健康和生物技术具有重要作用。两个例子是与人体相关的许多微生物（例如，肠道微生物组）和有助于土壤肥力和植物健康的物种。这些包含许多不同物种的天然微生物联合体通常由特征不明显的微生物组成。它们也有复杂的化合物和代谢物信号网络，在社区成员之间交换。自然联盟的复杂性使它们难以研究，并且可能模糊许多不同社区基础的共同原则的识别。因此，许多基本问题仍然是关于如何组织微生物财团，以保持生产力和弹性，在面对动态的环境条件。本项目利用人工微生物群落，这些群落相对简单，由特征明确的微生物组成。选择人工群落的这些特征是为了促进调查，从而深入了解指导微生物群落结构和功能的基本原理。这些研究活动增加了对微生物群落相互作用动力学的认识，潜在地提高了设计微生物群落的能力。该研究还为自然微生物共生的进化提供了见解。通过该项目培养研究生2名，博士后1名。此外，还有多个本科生研究体验机会。该项目还包括促进公共论坛的发展，以讨论生物工程的潜在利益和伦理问题。这些论坛在底特律的密歇根科学中心举办。研究小组正在使用一种蓝藻（长聚球菌PCC 7942），这种细菌可以从光和二氧化碳中产生并分泌大量的蔗糖。PI已经证明了多种其他微生物可以在相同的培养基中以“模块化”的方式培养。在这种情况下，共同培养的伙伴消耗蓝藻产生的蔗糖。这些人工微生物群落设计的灵活性允许不同的异养细菌与蓝藻一起培养。通过这种方式，确定了共培养物种之间的共同主题和相互作用机制。包括理性工程、正向遗传学、定向进化、代谢建模和基于个体的模拟在内的方法被用于识别物种之间交换的代谢物和信号。这些方法也用于确定代谢物交换如何促进财团的稳健性。所获得的知识用于合理设计微生物群落，使其在面对环境压力（如“不合作”微生物物种的入侵）时更加健壮。预计该提案的研究工作将为支持自然微生物共生的基本相互作用提供见解，并对环境可持续的蓝藻生物技术的发展产生转化影响。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

Microbial communities contribute important functions towards human health and biotechnology. Two examples are the many microbes associated with the human body (e.g., gut microbiome) and species that contribute to soil fertility and plant health. These natural microbial consortia that contain many different species, are often composed of poorly-characterized microbes. They also have complicated signaling networks of compounds and metabolites that are exchanged between community members. The complexity of natural consortia makes them difficult to study and can obscure identification of common principles that underlie many different communities. Consequently, many fundamental questions remain about how microbial consortia are organized to maintain productivity and resilience in the face of dynamic environmental conditions. This project makes use of artificial microbial communities that are relatively simple and composed of well-characterized microbes. These features of the artificial communities are chosen to facilitate an investigation that would lead to insight into underlying principles that guide the structure and function of microbial communities. The research activities increase knowledge of interaction dynamics in microbial communities, potentially improving the ability to engineer microbial consortia. The research also provides insight into the evolution of natural microbial symbioses. Through this project two graduate students and one postdoctoral fellow are trained. In addition, there are multiple undergraduate research experience opportunities. The project also involves promoting the development of public forums for the discussion of potential benefits and ethical concerns of bioengineering. These forums are hosted in the Michigan Science Center in Detroit.The research team is using a cyanobacterium (Synechococcus elongatus PCC 7942) that produces and secretes large quantities of sucrose from light and CO2. The PI has demonstrated that a variety of other microbes can be cultivated in the same media in a "modular" fashion. In these circumstances the co-cultured partner consumes the sucrose produced by the cyanobacteria. The flexibility in the design of these artificial microbial communities allows different heterotrophic bacteria to be cultivated with the cyanobacterium. In this way, common themes and mechanisms of interaction between the co-cultured species are identified. Approaches that include rational engineering, forward genetics, directed evolution, metabolic modeling, and individual-based simulations are used to identify the metabolites and signals exchanged between species. These approaches are also used to determine how metabolite exchanges contribute to consortia robustness. The knowledge gained is used to rationally design microbial communities that are more robust in the face of environmental pressures, such as invasion by "non-cooperating" microbial species. It is anticipated that the research efforts from this proposal will provide insights into fundamental interactions underpinning natural microbial symbioses, with translational impacts for the development of environmentally-sustainable cyanobacterial biotechnologies.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.